di Martino, Orsola (2015) Identification and characterization of novel activities from plant stem cell extracts regulating epidermal cell proliferation and homeostasis. [Tesi di dottorato]

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My PhD program included two phases, the first was carried out in the laboratory of Molecular Genetics, under the supervision of Professor Viola Calabrò, and the latter in the laboratory of Arterra Biosciene Srl. Arterra Bioscience is an Italian research-based biotech company with a strong know-how in biological science and an extensive experience in screening for the discovery of active molecules. The opportunity to join these two different scientific groups allows me to gain a more comprehensive experience including molecular biology and industrial biotechnology. During my period in Arterra Bioscience Srl, I investigated whether Betula pendula and Hybiscus syriacus plant stem cells could have beneficial effects on several aspects of skin homeostasis. Surprisingly, I found that Betula p. extract can be a valuable bioactive ingredient to use in cosmetic field for improving skin hydration, on other hand Hibiscus s. extract turned out to be more efficient in stimulating skin regeneration. The research about skin regeneration and differentiation is not only an appealing topic for biotechnological company, but also for molecular basic investigation. Indeed, in the laboratory of the professor Viola Calabrò, I had the possibility to study the molecular mechanisms governing skin regeneration and differentiation. The epidermis is the outermost layer of the skin, a multistratified epithelium whose homeostasis depends on a balance between cell proliferation and differentiation. Np63 is a critical pro-proliferative factor and a marker of epidermal stemness. We had previously shown that Np63 physically interacts with YB-1 a multifunctional protein with a well assessed oncogenic potential (Di Costanzo et al. 2012). Given the great potential that YB-1 may have in the control of keratinocyte proliferation, I have investigated in more details the functional relationships between YB-1 and Np63 and provided clear evidences indicating that Np63 plays a role in the control of YB-1 protein stability and turnover (di Martino et al. 2015 in submission). Finally, I spent a period of four months abroad at the Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany (April 2014- July 2014) under the supervision of Professor Nicholas S. Foulkes, one of the major expert in zebrafish biology. During this period I demonstrated that YBX-1 protein is expressed in adult zebrafish fins and in the embryonic cell line (Pac2). Moreover, I obtained consistent evidences that YBX-1 nuclear localization and protein expression level is a circadian regulated protein. Indeed, under a light-dark cycle it shows a maximum peak of nuclear protein at the beginning of the light phase and a minimum trough during the beginning of the dark phase. All these working experiences gave me the possibility to study different aspects of skin proliferation and differentiation, developing new bioactive molecules to use in the cosmetics field and studying more in detail the molecular mechanisms that regulate keratinocyte proliferation and differentiation.

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